1. Field of the Invention
The present invention relates to the field of biomedical engineering and medical treatment of diseases and disorders. More specifically, the invention relates to methods for destroying aberrant cells, including tumor tissues, using a series of electrical pulses having durations on the nanosecond scale.
2. Description of Related Art
Treatment of abnormal cell growth in or on normal body tissues and organs can be achieved in many different ways to achieve reduced aberrant cell growth and even destruction of an aberrant cell mass. In general, treatments known in the art involve surgical intervention to physically remove an aberrant cell mass or tissue comprised of tumor cells, radiation to kill aberrant cells, exposure of aberrant cells to toxic chemicals (i.e., chemotherapy), or a combination of two or all three of these. While each treatment modality has shown significant effectiveness in treatment of various cell proliferative diseases, no one technique has been shown to be highly effective at treating all types of cell proliferative diseases and disorders. Furthermore, each technique has significant drawbacks. For example, surgical intervention is highly effective at removal of solid tumors on tissues and organs that are physically accessible and capable of sustaining physical damage or capable of regeneration. However, surgical intervention can be difficult to perform on tumors that are not readily accessible or on organs that do not regenerate, and can involve substantial physical damage to the patient, requiring extensive recuperation times and follow-on treatments. Likewise, treatment with radiation can result in undesirable collateral damage to tissue surrounding the tumor, and can cause long-lasting side-effects, which can lower the quality of life of the patient. Similarly, chemotherapeutic treatments cause systemic damage to the patient, and can result in significant side-effects that might require a long recuperation period or permanent damage to the patient.
Recently, electric pulse therapies, which are initiated by exposing cells or tissues to electric fields, have been studied for cancer treatment in the form of electroporation. In addition to the suffix “poration”, the terms “breakdown” and “permeabilization” have been used to characterize this phenomenon, in which the application of certain short direct current (DC) or alternating current (AC) electric fields can result in an increase in the permeability of a cell's plasma membrane and intracellular membranes. As a function of the induced transmembrane potential (the electric potential difference across the plasma membrane), the pulse can have no effect on the plasma membrane, reversibly permeabilize the plasma membrane after which cells can survive (reversible electroporation), or irreversibly permeabilize the plasma membrane in a manner that leads to cell death, presumably through a loss of homeostasis (irreversible electroporation or IRE). It is generally accepted that IRE occurs if the induced transmembrane voltage reaches a value of about one volt at room temperature. In IRE procedures for inducing cell death, the pulse amplitude is typically on the order of hundreds of volts. The pulse duration employed in IRE is longer than the charging time of the plasma membrane, which is typically taken to be around one microsecond. Supra-poration is a type of electroporation that occurs when the electric pulse duration used is in the nanosecond time range, and shorter than the charging time of the plasma membrane of a target cell. When this occurs, cell death is no longer a consequence primarily of irreversible plasma membrane permeabilization. Rather, it is at least partially the result of structural deformation of intracellular organelles. In electroporation, the voltages are applied in order to electroporate tissue without inducing significant Joule heating, which would significantly damage major blood vessels and the extracellular matrix, as well as surrounding healthy tissue. For a specific tissue type and set of pulse conditions, the primary parameter determining the volume that undergoes electroporation is the electric field distribution within the tissue. Typically, electroporation is induced by applying 100 us or 20 ms pulses.
Although advances have been made recently in the use of electric pulses to induce cell death, there still exists a need in the art for improved methods for destroying diseased or disordered tissues, such as tumor tissues. The present invention addresses those needs.